title: A novel KCNA1 mutation identified in an Italian family affected by episodic ataxia type 1.
abstract: Episodic ataxia type 1 (EA1) is a rare human neurological syndrome characterized by continuous myokymia and attacks of generalized ataxia that can be triggered by abrupt movements, emotional stress and fatigue. An Italian family has been identified where related members displayed continuous myokymia, episodes of ataxia, attacks characterized by myokymia only, and neuromyotonia. A novel missense mutation (F414C), in the C-terminal region of the K(+) channel Kv1.1, was identified in the affected individuals. The mutant homotetrameric channels were non-functional in Xenopus laevis oocytes. In addition, heteromeric channels resulting from the co-expression of wild-type Kv1.1 and Kv1.1(F414C), or wild-type Kv1.2 and Kv1.1(F414C) subunits displayed reduced current amplitudes and altered gating properties. This indicates that the pathogenic effect of this KCNA1 mutation is likely to be related to the defective functional properties we have identified.
authors.affiliation: Section of Human Physiology, Department of Internal Medicine, University of Perugia School of Medicine, Via del Giochetto, I-06126 Perugia, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Imbrici
authors.forename: F
authors.initials: F
authors.lastname: Gualandi
authors.forename: M C
authors.initials: MC
authors.lastname: D'Adamo
authors.forename: M Taddei
authors.initials: MT
authors.lastname: Masieri
authors.forename: P
authors.initials: P
authors.lastname: Cudia
authors.forename: D
authors.initials: D
authors.lastname: De Grandis
authors.forename: R
authors.initials: R
authors.lastname: Mannucci
authors.forename: I
authors.initials: I
authors.lastname: Nicoletti
authors.forename: S J
authors.initials: SJ
authors.lastname: Tucker
authors.forename: A
authors.initials: A
authors.lastname: Ferlini
authors.forename: M
authors.initials: M
authors.lastname: Pessia
mesh_terms: D000328:Adult; D000818:Animals; D001259:Ataxia / Q000150:complications / Q000235:genetics*; D055592:Biophysical Phenomena; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D003545:Cysteine / Q000235:genetics; D004252:DNA Mutational Analysis; D004558:Electric Stimulation; D005192:Family Health; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D007558:Italy; D051662:Kv1.1 Potassium Channel / Q000235:genetics*; D051663:Kv1.2 Potassium Channel / Q000235:genetics; D008297:Male; D008564:Membrane Potentials / Q000235:genetics; D008845:Microinjections / Q000379:methods; D008958:Models, Molecular; D020125:Mutation, Missense / Q000235:genetics*; D020385:Myokymia / Q000150:complications / Q000235:genetics*; D009865:Oocytes; D018408:Patch-Clamp Techniques / Q000379:methods; D010649:Phenylalanine / Q000235:genetics; D029867:Xenopus Proteins / Q000235:genetics; D014982:Xenopus laevis; D055815:Young Adult
chemical_list: C496946:KCNA1 protein, human; D051663:Kv1.2 Potassium Channel; D029867:Xenopus Proteins; C084069:kcna1 protein, Xenopus; D051662:Kv1.1 Potassium Channel; D049452:Green Fluorescent Proteins; D010649:Phenylalanine; D003545:Cysteine